EXCITATORY AMINO-ACIDS (EAAS) STIMULATE PHOSPHATIDYLINOSITOL TURNOVER IN ADULT-RAT STRIATAL SLICES - INTERACTION BETWEEN NMDA AND EAA METABOTROPIC RECEPTORS

The effect of excitatory amino acids (EAAs) on phosphatidylinositol (PI) turnover in adult rat striatal slices was investigated. Quisqualic acid (QA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainic acid (KA), ibotenic acid (IBO) and N-methyl-D-aspartic acid (NMDA) maximally increased inositol phosphate (IF) formation at 10 mu M while trans-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) was maximally effective at 100 mu M. The NMDA channel blocker dizolcipine (MK-801) counteracted the effect of NMDA 10 mu M and IBO 10 mu M while it potentiated that of IBO 100 mu M and IBO 1000 mu M. Conversely, the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) prevented the effect of AMPA and KA and reduced that of QA (all at 10 mu M). Lowering extracellular Ca2+ concentrations ([Ca2+](0)) differentially affected the PI response to EAAs. The ACPD 30 mu M effect was unchanged at low [Ca2+](0) (but abolished when EGTA 2 mM was added), while that of ACPD 100 mu M was halved in 0.1 mM and almost abolished in a nominally free Ca2+ medium. NMDA 10 mu M and AMPA 10 mu M were ineffective at low [Ca2+](0) while NMDA 100 mu M, ineffective in a 1.2 mM Ca2+ medium, strongly stimulated IP formation in 0.1 mM Ca2+ but not in a nominally free Ca2+ medium. The effect of NMDA on EAA metabotropic receptor agonist stimulated PI turnover was also studied. NMDA 10 mu M potentiated the effect of ACPD 30 mu M. This positive cooperation persisted at low [Ca2+](0) but not in the presence of EGTA. Conversely, NMDA 100 mu M prevented the effect of ACPD 100 mu M, This negative interference was reversed when Ca2+ was omitted from the medium. This study shows that in the adult rat striatum both EAA metabotropic and ionotropic receptor activation increases IP formation. A positive and negative interaction between NMDA and metabotropic receptor activation was also found to regulate PI turnover. The role of[Ca2+](0) in subserving the PI response to EAAs was made evident.